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New quinazoline-N-4-fluorophenyl derivatives as potential anticancer agents: Discovery of a promising dual EGFR/VEGFR-2 inhibitor 作为潜在抗癌剂的新型喹唑啉-N-4-氟苯基衍生物:发现前景广阔的表皮生长因子受体/表皮生长因子受体-2双重抑制剂
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-04 DOI: 10.1016/j.jksus.2024.103518
Mohammed H. Geesi
This research is dedicated to synthesizing a new group of quinazoline-N-4-fluorophenyl 4a–d structures and evaluating their anticancer efficacy across multiple cancer cell lines. The molecular design of these derivatives was based on the structural features required for dual inhibition of VEGFR-2 and EGFR. The new derivatives were structurally characterised by NMR analyses. Cytotoxicity was assessed in this study against various cancerous cell strains. Among these, the top three products were further assessed for their capacity to block the enzymatic activity of (VEGFR-2) and (EGFR). Product 4b, in particular, exhibited a strong cytotoxic profile, with IC50 values of 68.2 ± 1.54 nM against EGFR and 189 ± 5.66 nM against VEGFR-2. Molecular docking studies demonstrated that compound 4b effectively interacts with the active sites of both VEGFR-2 and EGFR, potentially influencing its action pathway as a powerful inhibitor.
这项研究致力于合成一组新的喹唑啉-N-4-氟苯基 4a-d 结构,并评估它们在多种癌细胞系中的抗癌功效。这些衍生物的分子设计基于 VEGFR-2 和表皮生长因子受体(EGFR)双重抑制所需的结构特征。通过核磁共振分析对新衍生物进行了结构表征。这项研究评估了新衍生物对各种癌细胞株的细胞毒性。对其中前三种产品阻断(血管内皮生长因子受体-2)和(表皮生长因子受体)酶活性的能力进行了进一步评估。尤其是产品 4b,它具有很强的细胞毒性,对表皮生长因子受体的 IC50 值为 68.2 ± 1.54 nM,对血管内皮生长因子受体-2 的 IC50 值为 189 ± 5.66 nM。分子对接研究表明,化合物 4b 与血管内皮生长因子受体-2 和表皮生长因子受体的活性位点有效地相互作用,可能会影响其作为强效抑制剂的作用途径。
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引用次数: 0
Phytochemical composition and therapeutic potential of Caralluma edulis a cholistani plant 乔利斯坦人的一种植物 Caralluma edulis 的植物化学成分和治疗潜力
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-04 DOI: 10.1016/j.jksus.2024.103519
Bushra Gillani , Sarah Tariq , Mirza Imran Shahzad , Tatheer Fatima , Marcello Locatelli , Xinxia Cai , Adnan Noor Shah , Ajaz Ahmad
This study explores C. edulis, a plant indigenous to the Cholistan desert, locally known as Pimpa or Seetu, traditionally consumed as a vegetable. Our research aimed to comprehensively analyze its phytochemical constituents, and evaluate its antibacterial, antioxidant, antiviral, anti-inflammatory, antidiabetic, and antipyretic potentials. Utilizing a range of extracts including methanol (MtOH), ethanol (EtOH), ethyl acetate (EA), n-hexane (n-hex), dichloromethane (DCM), and aqueous (Aq), for effective extraction of phytochemicals from C. edulis. Standard biochemical assays and High-Performance Liquid Chromatography-Photodiode Array (HPLC-PDA) were used for analysis of phenolic compounds. Antibacterial effect(s) were confirmed through disc diffusion method and min inhibitory concentrations (MICs). The antioxidant activity was assessed through the Ferric Reducing Antioxidant Power (FRAP) assay and the DPPH radical scavenging method. In vivo antiviral potential was assessed through Hemagglutination (HA) test. Anti-inflammatory, antidiabetic, and antipyretic activities were performed on female albino rats using carrageenan, alloxan monohydrate and yeast-induced methods, respectively. Statistical analysis was done using standard one way ANOVA.Our findings revealed a rich diversity of phenolic compounds and the presence of proteins, alkaloids, and carbohydrates in C. edulis. MtOH and n-hex extracts demonstrated deep antiviral activity against various viral strains. In vivo toxicology studies indicated no significant toxicity at doses up to 5 g/kg. The DCM extract has shown notable anti-inflammatory effects, and EA extract was leading in antipyretic activity. All extracts, except MtOH, exhibited antidiabetic properties.In conclusion, C. edulis emerges not only as a valuable nutritional source but also as a potent alternative medicinal resource, offering wide range of therapeutic benefits.
本研究探讨了乔里斯坦沙漠中的一种本土植物 C. edulis,当地人称其为 Pimpa 或 Seetu,传统上作为蔬菜食用。我们的研究旨在全面分析其植物化学成分,并评估其抗菌、抗氧化、抗病毒、抗炎、抗糖尿病和解热潜力。利用一系列提取物,包括甲醇(MtOH)、乙醇(EtOH)、乙酸乙酯(EA)、正己烷(n-hex)、二氯甲烷(DCM)和水(Aq),从 C. edulis 中有效提取植物化学物质。酚类化合物的分析采用了标准生化测定法和高效液相色谱-光电二极管阵列(HPLC-PDA)法。通过盘扩散法和最低抑菌浓度(MICs)确认了抗菌效果。抗氧化活性通过铁还原抗氧化力(FRAP)测定法和 DPPH 自由基清除法进行评估。体内抗病毒潜力通过血凝试验(HA)进行评估。使用卡拉胶、一水阿脲和酵母诱导法分别对雌性白化大鼠进行了抗炎、抗糖尿病和解热活动的研究。我们的研究结果表明,C. edulis 中含有丰富多样的酚类化合物以及蛋白质、生物碱和碳水化合物。MtOH和n-hex提取物对各种病毒株具有很强的抗病毒活性。体内毒理学研究表明,在剂量高达 5 克/千克时没有明显的毒性。DCM 提取物具有明显的抗炎作用,而 EA 提取物在解热活性方面处于领先地位。总之,C. edulis 不仅是一种宝贵的营养来源,也是一种有效的替代药物资源,具有广泛的治疗功效。
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引用次数: 0
Ginkgetin alleviates polystyrene microplastics-instigated liver injury in rats through Nrf-2/Keap-1 pathway activation 银杏黄酮通过激活 Nrf-2/Keap-1 通路减轻聚苯乙烯微塑料引发的大鼠肝损伤
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-03 DOI: 10.1016/j.jksus.2024.103515
Naila Ghafoor , Kainat Fatima , Moazama Batool , Muhammad Imran , Shaik Althaf Hussain , Usman Atique
Polystyrene microplastics (PS-MPs) are potential environmental toxicants that are reported to instigate oxidative stress (OS) in the liver. Ginkgetin (GK) is a natural biflavonoid with potential therapeutic activities. This experiment was executed to access the putative effect of GK against PS-MPs provoked hepatotoxicity. Four groups were formed from 48 rats including control, PS-MPs (0.01 mg/kg) group, PS-MPs (0.01 mg/kg) + GK (25 mg/kg) co-treated group and GK (25 mg/kg) alone group. The exposure of PS-MPs markedly decreased the expressions of antioxidant genes and Nrf-2, besides escalating Keap-1 expression. It also decreased the activities of antioxidants i.e., glutathione (GSH), glutathione S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), glutathione reductase (GSR), while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) contents. Additionally, a notable escalation in hepatic serum markers i.e., alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate aminotransferase (AST) level was observed. Furthermore, PS-MPs exposure escalated the levels of inflammatory markers, i.e., tumor necrosis factor-α (TNF-α), interleukin- 6 (IL-6), nuclear factor-kappa B (NF-kB), interleukin-β (IL-1β) level and cyclooxygenase-2 (COX-2) activity. PS-MPs treatment augmented Caspase-3 and Bax expressions and decreased Bcl-2 expression. Nevertheless, GK treatment notably abated PS-MPs prompted liver injuries owing to its hepatoprotective efficacy.
聚苯乙烯微塑料(PS-MPs)是一种潜在的环境毒物,据报道会引发肝脏氧化应激(OS)。银杏黄酮(GK)是一种具有潜在治疗活性的天然双黄酮类化合物。本实验旨在了解 GK 对 PS-MPs 引起的肝毒性的潜在作用。48 只大鼠分成四组,包括对照组、PS-MPs(0.01 毫克/千克)组、PS-MPs(0.01 毫克/千克)+ GK(25 毫克/千克)联合处理组和 GK(25 毫克/千克)单独处理组。暴露于 PS-MPs 后,抗氧化基因和 Nrf-2 的表达明显下降,Keap-1 的表达也有所上升。它还降低了谷胱甘肽(GSH)、谷胱甘肽 S-转移酶(GST)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、血红素加氧酶-1(HO-1)、超氧化物歧化酶(SOD)和谷胱甘肽还原酶(GSR)等抗氧化剂的活性,同时增加了活性氧(ROS)和丙二醛(MDA)的含量。此外,还观察到肝脏血清指标,即碱性磷酸酶(ALP)、丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)水平明显升高。此外,接触 PS-MPs 会使炎症标志物水平升高,即肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、核因子-kappa B(NF-kB)、白细胞介素-β(IL-1β)水平和环氧化酶-2(COX-2)活性。PS-MPs 处理增加了 Caspase-3 和 Bax 的表达,降低了 Bcl-2 的表达。然而,由于 GK 具有保护肝脏的功效,它能显著减轻 PS-MPs 对肝脏的损伤。
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引用次数: 0
Novel drug delivery to the brain for neurodegenerative disorder treatment using carbon nanotubes 利用碳纳米管向大脑输送新型药物,治疗神经退行性疾病
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1016/j.jksus.2024.103513
Mohammed Al-zharani , Md Saquib Hasnain , Mohammed S. Al-Eissa , Reem A. Alqahtani
Neurodegenerative disorders pose a significant challenge in drug delivery because of the substantial obstacle presented by the blood–brain barrier (BBB). Conventional therapeutic agents frequently encounter constraints in efficiently penetrating the brain, thus requiring inventive delivery strategies. This review explores the potential aspects of the carbon nanotubes (CNTs) as an advanced drug delivery system for treating neurodegenerative disorders. CNTs, with their distinctive structural and physicochemical characteristics, present an intriguing framework for addressing challenges related to drug delivery across the BBB. The review emphasizes the functionalization of CNTs, utilizing diverse chemical modification techniques to improve their biocompatibility and effectiveness as drug carriers. The variations have a significant effect on crucial factors related to the growth of neurons.
Moreover, the review emphasizes the therapeutic ability of CNTs in treating neurodegenerative disorders. By introducing purified CNT substrates, an increase in the growth of dendrites and improved adhesion of hippocampal neurons was reported. This has led to significant progress in the processing of neuronal signals and the development of neural circuits. Finally, this review offers in-depth understanding of the innovative and enhanced nano-scaffolds provided by CNTs for transporting therapeutic substances to the brain. This offers potential for more efficient treatments for neurodegenerative disorders.
由于血脑屏障(BBB)带来的巨大障碍,神经退行性疾病给药物输送带来了巨大挑战。传统的治疗药物在有效穿透大脑方面经常遇到限制,因此需要创新的给药策略。本综述探讨了碳纳米管(CNTs)作为一种先进的给药系统在治疗神经退行性疾病方面的潜力。碳纳米管具有独特的结构和理化特性,为应对跨 BBB 给药的挑战提供了一个有趣的框架。综述强调了利用各种化学修饰技术对碳纳米管进行功能化处理,以提高其生物相容性和作为药物载体的有效性。此外,综述还强调了 CNT 在治疗神经退行性疾病方面的治疗能力。据报道,通过引入纯化的碳纳米管基底,海马神经元的树突生长和粘附性得到了改善。这在神经元信号处理和神经回路开发方面取得了重大进展。最后,本综述深入介绍了由 CNT 提供的创新和增强型纳米支架,用于向大脑输送治疗物质。这为更有效地治疗神经退行性疾病提供了潜力。
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引用次数: 0
Earthquake risk assessment for Kuwait City, Kuwait 科威特科威特城地震风险评估
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1016/j.jksus.2024.103514
Abd el-aziz Khairy Abd el-aal , Farah Al-Jeri , Abdullah Al-Enezi , Shaimaa Ismail Mostafa
Estimating the expected losses from a seismic disaster, whether economic or human is considered one of the most important priorities for urban development in countries, especially those with continually expanding urban areas, high-rise buildings, and skyscraper construction as is the case in Kuwait City. It is necessary to conduct an earthquake risk assessment study due to Kuwait’s geographical location which makes it close to the most important global seismic belt, the Zagros Seismic Belt, and its proximity to local seismic sources. To conduct such a study, three inputs including seismic hazard, exposure, and vulnerability modules were incorporated, considering the inputs’ uncertainty. To assess the seismic hazard module, a unified earthquake catalog was compiled, a seismotectonic model of 27 seismic sources was designed, the recurrence parameters of seismicity and the strongest predictable earthquake were calculated for each source, and the unified hazard spectrums were obtained. Earthquake scenarios were generated to create a seismic hazard module. The exposure module is performed using data from the Kuwaiti Public Authority for Civil Information including coordinates of 33,066 facilities and buildings, area, height, shape, and type of buildings, the materials used in their construction, their occupancy, and replacement cost. The vulnerability module was implemented using mean damage ratio curves by choosing the most appropriate equations that describe the condition of buildings in Kuwait, the vast majority of which are modern multi-story concrete buildings. The final results including the economic losses of the exposures were calculated using probabilistic metrics (predicted annual losses, loss exceedance curve, and probable maximum loss). The results showed that the annual average loss is $12,793,319.52 and that seismic source No.27 to the north of Kuwait has a significant value to the losses, but the frequent occurrence of losses from seismic source No.15 to the east of Kuwait, in the Zagros region, gave the most danger to Kuwait. Seismic risk results can be used to create emergency response scenarios and risk mitigation strategies.
估算地震灾害的预期损失,无论是经济损失还是人员损失,都被认为是各国城市发 展最重要的优先事项之一,特别是像科威特城这样城市面积不断扩大、高层建筑和摩天大楼 不断增多的国家。科威特的地理位置靠近全球最重要的地震带--扎格罗斯地震带,而且靠近当地的震源,因此有必要进行地震风险评估研究。为了进行这样的研究,考虑到输入的不确定性,纳入了三个输入,包括地震灾害、暴露和脆弱性模块。为评估地震灾害模块,编制了统一的地震目录,设计了包含 27 个震源的地震构造模型,计算了每个震源的地震重现参数和可预测的最强地震,并获得了统一的灾害谱。生成地震场景,创建地震灾害模块。暴露模块使用科威特民事信息公共管理局提供的数据,包括 33 066 个设施和建筑物的坐标、建筑物的面积、高度、形状和类型、建筑材料、占用率和重置成本。脆弱性模块是通过选择描述科威特建筑物状况的最合适方程,使用平均损坏率曲线来实 施的,其中绝大多数是现代多层混凝土建筑。最终结果包括使用概率指标(预测年损失、损失超额曲线和可能的最大损失)计算的风险经济损失。结果表明,年平均损失为 12,793,319.52 美元,科威特北部的第 27 号地震源对损失的影响很大,但科威特东部扎格罗斯地区的第 15 号地震源频繁发生的损失对科威特的危害最大。地震风险结果可用于制定应急方案和风险缓解战略。
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引用次数: 0
Organic farming innovations: Cultivation of wheatgrass microgreens in soil enriched with fruit peels and antimicrobial assessment 有机农业创新:在富含果皮的土壤中栽培小麦草微型灌木并进行抗菌评估
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-31 DOI: 10.1016/j.jksus.2024.103511
Krithika R, Raajeswari P.A

Objective

This study explores the viability of fruit peel-enriched soils as a sustainable growth medium, acting as a biofertilizer for wheatgrass microgreens. Additionally, the research seeks to evaluate the antimicrobial properties of fruit peels, typically considered agricultural waste, to determine their influence on plant growth parameters.

Methods

Fruit peels from pomegranate, orange, and sweet lime were collected and processed into powder, and diluted with water to create enriched soil. Wheatgrass microgreens were cultivated in conventional potting soil and soil enriched with fruit peel powder. Growth parameters, including germination rates, shoot and root length, and total yield of wheatgrass microgreens, were monitored over a 15-day growth cycle. Antimicrobial analysis was conducted on selected fruit peels, assessing their impact on Staphylococcus aureus and Escherichia coli compared to a control (Rifampicin).

Results

The results, analyzed through ANOVA and Tukey (post hoc) tests, indicate significant differences among fruit peel-enriched soils. Pomegranate peel emerged as a particularly effective enhancer of wheatgrass microgreen growth. Furthermore, the antimicrobial analysis revealed that pomegranate and sweet lime peels exhibited superior properties, with a notable zone of inhibition effects on Staphylococcus aureus and Escherichia coli compared to the control (Rifampicin).

Conclusion

This study demonstrates the potential of fruit peels as effective biofertilizers to promote wheatgrass microgreen growth in sustainable agricultural practices. The multifaceted benefits include enhanced crop development and the discovery of natural antimicrobial agents, particularly in pomegranate and sweet lime peels. These findings support the broader adoption of environmentally conscious approaches in agriculture, emphasizing the value of utilizing agricultural waste for plant growth promotion and the development of natural alternatives to synthetic antimicrobial agents.
目的本研究探讨了富含果皮的土壤作为可持续生长介质的可行性,这种土壤可作为小麦草微型灌木的生物肥料。此外,研究还试图评估果皮(通常被认为是农业废弃物)的抗菌特性,以确定其对植物生长参数的影响。方法收集石榴、橙子和甜酸橙的果皮,将其加工成粉末,然后用水稀释,制成富集土壤。在常规盆栽土壤和富含果皮粉的土壤中栽培小麦草。在 15 天的生长周期内对小麦草的生长参数进行监测,包括发芽率、芽和根的长度以及小麦草的总产量。对选定的果皮进行了抗菌分析,评估它们与对照组(利福平)相比对金黄色葡萄球菌和大肠杆菌的影响。石榴皮对小麦草微绿生长的促进作用尤为明显。此外,抗菌分析表明,与对照组(利福平)相比,石榴皮和甜酸橙皮表现出更优越的特性,对金黄色葡萄球菌和大肠杆菌有明显的抑制作用。其多方面的益处包括促进作物生长和发现天然抗菌剂,特别是石榴皮和甜酸橙皮中的天然抗菌剂。这些发现支持在农业中更广泛地采用具有环境意识的方法,强调了利用农业废弃物促进植物生长和开发合成抗菌剂天然替代品的价值。
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引用次数: 0
Rapid diagnostics for monitoring chronic kidney disease aggravated as a post COVID complication 监测因 COVID 后并发症而恶化的慢性肾病的快速诊断方法
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-29 DOI: 10.1016/j.jksus.2024.103490
Priya Paliwal , Dignya Desai , Nemat Ali , Mohammad Khalid Parvez , Mohammad Rizwan Alam , Kyung Jin Seo , Manali Datta
The prevalence of chronic kidney disease (CKD) is increasing, affecting more than 10 % of the global population. In addition, subclinical inflammation associated with COVID-19 infection leads to a progressive decline in kidney function, resulting in chronic kidney disease. Early intervention in candidates with early-stage CKD may delay, or avert, progression to end-stage complications. It is widely accepted that serum Cystatin C is a reliable and early indicator of CKD. Urinary Cystatin C tends to increase with the progression of kidney malfunctioning. Thus, early detection can lower the morbidity and mortality associated with CKD. This study includes the design of a proteotronic platform for the rapid detection of CKD. Here, we have developed a biosensor that is highly specific to Cystatin C and shows a negligible response to other urinary biomarkers. The sensitivity of the biosensor was 50889.6 µA cm−2 mg−1 and the limit of detection  for Cystatin C in the sample was calculated as 26 ng mL−1. The stability of the biosensor was studied by measuring the change inthe differential pulse voltammetric current at every month of storage at 4 °C. The biosensor was established to be stable for 12 months, with approximately 10 % loss in the preliminary peak current (Ip) value with storage at 4 °C. Thus, the fabricated proteotronic biosensor exhibited an analytical yet simple approach for point of care diagnostics (POCD) of CKD. The developed POCD is economical and proficient, and will enable CKD management in non-hospitalized patients.
慢性肾脏病(CKD)的发病率正在上升,影响着全球超过 10% 的人口。此外,与 COVID-19 感染相关的亚临床炎症会导致肾功能逐渐下降,从而引发慢性肾病。对早期慢性肾脏病患者进行早期干预可延缓或避免发展为终末期并发症。人们普遍认为,血清胱抑素 C 是 CKD 可靠的早期指标。尿胱抑素 C 会随着肾功能衰竭的进展而增加。因此,早期检测可降低与 CKD 相关的发病率和死亡率。这项研究包括设计一个用于快速检测 CKD 的蛋白质电子平台。在这里,我们开发了一种生物传感器,它对胱抑素 C 具有高度特异性,对其他尿液生物标志物的反应微乎其微。该生物传感器的灵敏度为 50889.6 µA cm-2 mg-1,样本中胱抑素 C 的检测限为 26 ng mL-1。通过测量在 4 °C 下储存一个月后差分脉冲伏安电流的变化,研究了生物传感器的稳定性。结果表明,该生物传感器在 4 °C下储存 12 个月后仍保持稳定,初步峰值电流(Ip)值的损失率约为 10%。因此,所制造的蛋白电子生物传感器展示了一种用于慢性肾脏病护理点诊断(POCD)的分析性简便方法。所开发的 POCD 既经济又熟练,将有助于对非住院病人进行 CKD 管理。
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引用次数: 0
Transcriptomic insights into skin cancer: A bioinformatics and network biology approach to biomarker identification 皮肤癌转录组学研究:用生物信息学和网络生物学方法识别生物标志物
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-29 DOI: 10.1016/j.jksus.2024.103510
Majji Rambabu , M. Navanneth Gowda , Prasanna Kumar Selvam , Karthick Vasudevan , K.R. Dasegowda , Parameswaran Saravanan , Karunakaran Rohini
Skin cancer is a widespread malignancy that primarily affects light-skinned populations globally, categorized into melanoma and non-melanoma skin cancers (NMSCs). Basal cell carcinoma and squamous cell carcinoma are the most common subtypes within NMSCs, with the global incidence of NMSCs projected to reach 2–3 million cases annually across regions like Europe, Canada, the USA, and Australia. Despite this prevalence, the genetic mechanisms behind skin cancer remain poorly understood. This study presents a novel gene discovery approach, leveraging transcriptome data from Next-Generation Sequencing datasets sourced from the European Nucleotide Archive to uncover new genes and pathways linked to skin cancer. The novelty of this research lies in its comprehensive approach that combines differential gene expression analysis with gene network and pathway enrichment analysis to identify actionable therapeutic targets. By utilizing bioinformatics tools such as DESeq2, Gene Set Enrichment Analysis (GSEA), and Cytoscape, we revealed critical gene interactions and pathways that have been underexplored in the context of skin cancer. Following rigorous quality control using FastQC and transcriptome-seq data alignment to the human genome (hg38), we identified 19 differentially expressed genes, including 2 down-regulated and 17 up-regulated. Key genes such as IL6, CCND2, PLAUR, and CD44 were found to be involved in important pathways like IL6_JAK_STAT3_SIGNALING, ANGIOGENESIS, and APICAL_SURFACE. These findings provide valuable insights into skin cancer pathogenesis and offer potential therapeutic targets, laying the groundwork for future research aimed at improving treatment outcomes.
皮肤癌是一种广泛存在的恶性肿瘤,主要影响全球浅肤色人群,分为黑色素瘤和非黑色素瘤皮肤癌(NMSCs)。基底细胞癌和鳞状细胞癌是非黑素瘤皮肤癌中最常见的亚型,预计在欧洲、加拿大、美国和澳大利亚等地区,非黑素瘤皮肤癌的全球发病率每年将达到 200-300 万例。尽管发病率如此之高,但人们对皮肤癌背后的遗传机制仍然知之甚少。本研究提出了一种新颖的基因发现方法,利用来自欧洲核苷酸档案的下一代测序数据集的转录组数据,发现与皮肤癌相关的新基因和通路。这项研究的新颖之处在于它采用了综合方法,将差异基因表达分析与基因网络和通路富集分析相结合,以确定可操作的治疗靶点。通过利用 DESeq2、基因组富集分析(Gene Set Enrichment Analysis,GSEA)和 Cytoscape 等生物信息学工具,我们揭示了在皮肤癌方面尚未得到充分探索的关键基因相互作用和通路。在使用 FastQC 和转录组-序列数据与人类基因组(hg38)比对进行严格的质量控制后,我们发现了 19 个差异表达基因,包括 2 个下调基因和 17 个上调基因。发现IL6、CCND2、PLAUR和CD44等关键基因参与了IL6_JAK_STAT3_SIGNALING、ANGIOGENESIS和APICAL_SURFACE等重要通路。这些发现为皮肤癌的发病机制提供了有价值的见解,并提供了潜在的治疗靶点,为今后旨在改善治疗效果的研究奠定了基础。
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引用次数: 0
Exploring the uncharted: Zinc and phosphate solubilization in Zn-P isolates from wheat rhizosphere inceptisols 探索未知领域:小麦根瘤际土壤中锌-磷分离物的锌和磷酸盐溶解作用
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-28 DOI: 10.1016/j.jksus.2024.103509
Renu Gupta , Ravi Kumar , Wahidah H. Al-Qahtani , Mostafa A. Abdel-Maksoud
This research delves into the untapped potential of phosphorous and zinc solubilizing rhizobacteria, known as Zn-P isolates, from wheat rhizosphere inceptisols. A total of thirty rhizosphere soil samples were collected, resulting in recovery of forty unique bacterial isolates. After initial screening, out of forty isolates, recovered on the basis of halozone formation on the nutrient agar medium. four were subjected to biochemical and further molecular identification. Four isolates, identified as Bacillus subtilis (Zn-P-1), Pseudomonas aureginosa (Zn-P-2), Staphylococcus aureus (Zn-P-3), and Methylobacterium organophyllum (Zn-P-4) through a set of 16S rRNA primers, forward (5́- GGATGAGCCCGCGGCCTA-3́) and reverse (5́- CGGTGTGTACAAGGCCCGG-3́), exhibited superior solubilization efficiency of phosphorous and zinc These strains were evaluated via in vitro and pot culture assays. The study found that Zn-P-1 demonstrated the highest zinc solubilization (134.87 mg/l) when ZnO was used as the zinc source as compared to ZnCO3 and Zn-EDTA as also highest at 72.32 mg/l in CaH2PO4 and lowest at 14.44 mg/l with KH2PO4 using P sources, thus highlighting the role of Bacillus in zinc and phosphorous activity with substrate type. The inoculation of tri-calcium phosphate (TCP) and ZnCO3, along with Bacillus and Methylobacterium, led to increased phosphorous and zinc solubilization, uptake, and use efficiency, marking these rhizobacteria as potentially beneficial for nutrient enhancement and PGPR activities in wheat crops grown in inceptisols.
这项研究深入探讨了小麦根瘤菌圈浸润土中磷锌增溶根瘤菌(又称 Zn-P 分离物)尚未开发的潜力。研究人员共采集了 30 个根瘤土壤样本,从中分离出 40 个独特的细菌。经过初步筛选,根据在营养琼脂培养基上形成卤酮的情况,从 40 个分离菌株中选出 4 个进行生化鉴定和进一步的分子鉴定。通过一组 16S rRNA 引物,四个分离物被鉴定为枯草芽孢杆菌(Zn-P-1)、金黄色假单胞菌(Zn-P-2)、金黄色葡萄球菌(Zn-P-3)和有机绿叶甲基杆菌(Zn-P-4)、正向(5́- GGATGAGCCCGCGGCCTA-3́)和反向(5́- CGGTGTGTACAAGGCCCG-3́)对磷和锌的溶解效率进行了评估。研究发现,与 ZnCO3 和 Zn-EDTA 相比,当使用氧化锌作为锌源时,Zn-P-1 的锌溶解度最高(134.87 毫克/升);使用 CaH2PO4 作为磷源时,Zn-P-1 的锌溶解度最高(72.32 毫克/升);使用 KH2PO4 时,Zn-P-1 的锌溶解度最低(14.44 毫克/升)。在接种磷酸三钙(TCP)和 ZnCO3 以及芽孢杆菌和甲基芽孢杆菌后,磷和锌的溶解、吸收和利用效率均有所提高,这表明这些根瘤菌可能有益于小麦作物的养分强化和 PGPR 活性。
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引用次数: 0
Investigating the colon toxicity and carcinogenic role of monosodium glutamate compared with Dimethylhydrazine in male Wistar rats: Exploring the link to childhood colon cancer risk 研究谷氨酸钠与二甲基肼对雄性 Wistar 大鼠结肠的毒性和致癌作用的比较:探索与儿童结肠癌风险的联系
IF 3.7 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-10-26 DOI: 10.1016/j.jksus.2024.103507
Meenakshi Sundari Rajendran , Selvaraj Jayaraman , Javed Masood Khan , Sharmila Jasmine , RajKumar Prabhakaran , Manikandan Vani Raju , Meenakshi Kaniyur Chandrasekaran , Rathi Muthaiyan Ahalliya , Poornima Kannappan , Chella Perumal Palanisamy , Gopalakrishnan Velliyur Kanniappan

Background

Colon cancer is rising among younger population than elder people. About 50% of colon cancer cases attributed to dietary factors. Monosodium glutamate (MSG) widely used taste enhancer prevalent in fast foods and processed items.

Objectives

The study investigated into the potential toxic and carcinogenic role of MSG in male Wistar rats of 1–3 months old and compared the effects with the Dimethyl hydrazine (DMH): by observing survival probability, estimation of serum biochemical parameters, and analysis for colon beta catenin protein expression.

Methods

Rats were grouped into control, DMH (s.c), low- and high dose MSG (LDMSG, HDMSG) (p.o). Survival rate statistically calculated using Kaplan-Meier plots and Log-rank tests. Biochemical analyses were done using standard protocols and one-way ANOVA were performed for data analysis. Beta catenin protein expressions were studied using immunohistochemistry and western blotting.

Results

Our study emphasizes that high dose MSG consumed male Wistar rats cause high decline in survival rate compared to low dose MSG and DMH. Estimated serum biochemical parameters showed significantly increased oxidative stress, altered liver and kidney function markers, alongside elevated serum sodium, total cholesterol, triglycerides, LDL, and inflammatory markers. Observed, colon polyps formed in DMH and MSG rats. Rat’s colon immunohistochemistry study expressed β- catenin whereas Western blotting results confirmed the altered β- catenin and β-catenin phosphorylation ratios in cytosol and nuclear region were elevated in DMH-induced colon cancer (p value of 0.0002), MSG low dose (p value of 0.003) and high dose (p value of 0.01) statistically significant. These findings highlights declined survival probabilities and pronounced oxidative stress markers, organ function changes, disrupted lipid profiles, and increased nuclear β-catenin expression reveals the potential toxic and carcinogenic role of MSG is influencing colon cancer development in male Wistar rat models.

Conclusion

Based on the results, the study underscores the potential toxic and carcinogenic role of MSG, particularly at neoplastic stages of colon cancer in male Wistar rat models.
背景结肠癌在年轻人群中的发病率高于老年人。约 50%的结肠癌病例归因于饮食因素。谷氨酸一钠(味精)被广泛用于快餐和加工食品中的增味剂。方法将大鼠分为对照组、DMH 组(s.c)、低剂量和高剂量味精组(LDMSG、HDMSG)(p.o)。采用 Kaplan-Meier 图和对数秩检验统计计算存活率。生化分析采用标准方案,数据分析采用单因素方差分析。结果我们的研究强调,与低剂量味精和 DMH 相比,雄性 Wistar 大鼠摄入高剂量味精会导致存活率大幅下降。估计的血清生化指标显示,氧化应激明显增加,肝肾功能指标发生变化,血清钠、总胆固醇、甘油三酯、低密度脂蛋白和炎症指标升高。观察发现,DMH 和味精大鼠结肠息肉形成。大鼠结肠免疫组化研究显示,DMH 诱导的结肠癌中,β- catenin 表达,而 Western 印迹结果证实,β- catenin 和 β-catenin 在细胞膜和核区的磷酸化比率发生了改变(p 值为 0.0002),MSG 低剂量(p 值为 0.003)和高剂量(p 值为 0.01)具有统计学意义。这些发现凸显了味精对雄性 Wistar 大鼠模型结肠癌发展的潜在毒性和致癌作用。
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引用次数: 0
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Journal of King Saud University - Science
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